Coexistence of myasthenia gravis and lichen planus: A case report and systematic review of related case reports from 1971 to 2024

Key Clinical Message The co‐occurrence of myasthenia gravis (MG) and lichen planus (LP) is a rare phenomenon, with only 13 cases reported in the English literature between 1971 and 2024. Patients with MG or LP, regardless of the thymoma status, require close monitoring for other autoimmune diseases. Abstract Myasthenia gravis (MG) is an uncommon autoimmune disease, resulting in fatigable muscle weakness in the ocular, bulbar, and respiratory muscles, as well as muscles of the extremities. Lichen planus (LP) is an autoimmune mucocutaneous disease, presenting with pruritic and violaceous plaques on the skin and mucosal surfaces. So far, MG and LP co‐occurrence is only reported in anecdotal individuals. This study reports a patient with MG and LP and systematically reviews the English literature on this rare co‐occurrence from 1971 to 2024, indicating only 13 cases with similar conditions. A 67‐year‐old man presented with ocular and progressive bulbar symptoms, a year after being diagnosed with generalized LP. Laboratory evaluations were normal except for the high anti‐AchR‐Ab titer and a positive ANA titer. Neurologic examinations revealed asymmetric bilateral ptosis, weakness and fatigability in proximal muscles, and a severe reduction in the gag reflex. He was diagnosed with late‐onset, seropositive MG. The treatment included pyridostigmine (60 mg, three times daily), intravenous immunoglobulin (25 g daily for 5 days), and oral prednisolone. There was no evidence of thymoma in the chest x‐ray and CT scan without contrast. However, a CT scan with contrast was not performed due to the patient's unstable condition. A common autoimmune mechanism may underlie the unclear pathophysiology of MG and LP co‐occurrence, with or without thymoma. Patients with MG, LP, or thymoma require close monitoring and assessment for other possible autoimmune diseases.


| BACKGROUND
Myasthenia gravis (MG), is an autoimmune neurological disorder caused by autoantibodies attachment to nicotinic acetylcholine receptors (nAChR) at the neuromuscular junction (NMJ) of skeletal muscles. 1 This rare disorder has an incidence of 2.1 to 5.0 per million people per year and a prevalence of 7 to 20 per 100,000 people. 2 Fatigable weakness is the clinical hallmark of this disease, defined as fluctuating muscle weakness that exacerbates with activity and alleviates with rest. 1 Ocular symptoms, including ptosis, diplopia, photophobia, and blurry vision are also common features. 3Additionally, bulbar muscles can be involved in the course of MG, resulting in dysphagia, dysarthria, and dysphonia. 1G can be categorized according to its clinical manifestations, age at onset, and type of autoantibodies.There are five main categories for MG based on the clinical manifestations. 4Class I is defined as limited ocular involvement in the absence of other symptoms 4 ; class II, III, and IV are characterized by mild, moderate, and severe weakness affecting other than ocular muscles, with or without ocular muscle weakness of any severity, 4 and class V is characterized by the need for intubation. 4lasses II, III, and IV are further classified into "a" and "b" subgroups: subgroup "a" describes a predominant weakness in voluntary muscles (limbs or axial muscles), and subgroup "b" describes predominant oropharyngeal or respiratory impairment. 4Considering the age of onset, MG is categorized as early-onset (< 50 years) and late-onset (≥ 50 years). 5According to the types of autoantibodies (Ab), patients are classified into seropositive (positive for anti-acetylcholine receptor antibody [anti-AchR Ab]) and seronegative (negative for anti-AchR Ab), 6 accounting for 80% and 20% of patients with MG, respectively. 2Autoantibodies against musclespecific tyrosine kinase protein (Anti-MuSK-Ab) are produced by 20%-50% of seronegative patients, resulting in MuSK-associated MG. 1,2,5 Other subgroups, including lipoprotein-related protein 4 (LRP4)-associated MG (autoantibody against LRP4) and antibody-negative generalized MG (without detectable AChR, MuSK, or LRP4 antibodies) are also reported. 5,7arly in the presentation of possible MG, the focus of the differential diagnostic considerations primarily hinges on the initial signs and symptoms. 5,8,9Conditions that may mimic ocular myasthenia encompass thyroid ophthalmopathy, chronic progressive external ophthalmoplegia, myotonic dystrophy, and oculopharyngeal dystrophy, as well as brainstem and motor cranial nerve pathology. 5,8,9Bulbar symptoms of MG may resemble manifestations of motor neuron disease, obstructive lesions of the oropharynx, brainstem disorders (i.e., gliomas), or multiple cranial nerve palsies. 5,8,9iagnostic considerations for limb weakness symptoms associated with MG encompass motor neuron disease, chronic inflammatory demyelinating polyneuropathy, other motor neuropathies, Lambert-Eaton myasthenic syndrome (LEMS), and myopathies. 5,8,9While isolated respiratory involvement is uncommon in MG, it may also manifest in motor neuron disease and acid maltase deficiency myopathy. 5,8,9Lastly, several conditions may mimic generalized myasthenia, including generalized fatigue, motor neuron disease, and LEMS. 5,8,9Other differential diagnoses include cerebral venous thrombosis, 10 multiple sclerosis, 9 and posterior reversible encephalopathy syndrome. 11,12G treatment options fall into four main categories: symptomatic treatment (anticholinesterase agents), chronic and rapid immunomodulating therapies, and surgery (thymectomy). 13The choice of therapy depends on the severity and progression of the disease, as well as the time it takes for each therapy to show clinical effect. 13yridostigmine bromide is the primary medication used for symptomatic treatment. 13However, most patients eventually require immunotherapy.Immunomodulating therapies aim to control the underlying immune response in MG. 13 Chronic immunomodulating therapies, including glucocorticoids, azathioprine, cyclosporine, mycophenolate, and so forth, offer long-term benefits. 13Rapid immunomodulating therapies, including plasmapheresis and intravenous immune globulin (IVIG), provide faster relief but are typically used in specific situations, such as myasthenic crisis, before thymectomy, as a bridge to slower-acting treatments, or as an adjunct to other medications in refractory cases. 13Thymectomy is particularly beneficial for patients with nonthymomatous generalized seropositive MG, but its effects take months to years to develop. 13P is a rare idiopathic autoimmune inflammatory skin disease, affecting 0.5 to 1% of the population. 14lthough it may occur at any age, most patients present in the third or sixth decade of life. 15Classic LP is presented as "6 Ps" (planar, purple, polygonal, pruritic, papules, and plaques) mostly on the flexural surfaces of the extremities. 16LP could also affect other parts of the body, including cutaneous tissues other than skin (scalp, hair, nails) and mucus membranes (genitalia, esophagus, conjunctiva). 14,17Therefore, several variants are defined for LP, including oral, nail, linear, vulvovaginal, annular, atrophic, ulcerative, and generalized LP. 14 Notably, generalized LP has seldom been reported in the literature; 14 it is characterized by rapidly spreading and disseminated lesions on the trunk, extremities, and mucous membranes. 18,19LP might be found with other conditions of impaired immunity, including thymoma, [20][21][22][23][24][25][26][27][28] ulcerative colitis (UC), 29,30 alopecia areata, vitiligo, and other skin disorders. 23,24,30Furthermore, it has been shown to be correlated with hepatitis C virus (HCV) infection. 31,32n the present study, we discuss a rare coincidence of MG and LP in an elderly patient who had been diagnosed with generalized LP followed by the development of MG symptoms almost a year later.4][35][36] We have also conducted a systematic review of similar reports in the literature up until February 2024.

| Objectives and review questions
There were two objectives of this study.
1. Reporting a patient in our center who developed MG and LP within a year.2. Systematically reviewing the literature for studies addressing the co-occurrence of MG and LP.

| Study design, information sources, and search strategy
This study was conducted at an academic hospital complex affiliated with Tehran University of Medical Sciences (TUMS), Tehran, Iran, and approved by the ethics committee of the university.As the patient was deceased, written informed consent for participation and publication of this manuscript was obtained from the patient's next of kin.The case study is reported according to the Consensusbased Clinical Case Reporting Guideline Development (CARE) guidelines (Table S1).
For the second objective, we performed a comprehensive search for publications up till February 01, 2024, through MEDLINE (via PubMed), Scopus, and Web of Science database, using the following medical subject headings (MeSH) and/or Title/Abstract/Keywords: "myasthenia gravis," "myasthenia," "myasthenic," "lichen planus," "lichenoid."The detailed search strategy is presented in Table S2.Additional sources were identified through cross-referencing.

| Eligibility criteria
All original studies written in English that explored the coexistence of confirmed diagnoses of MG and LP were eligible to be included, regardless of the presence of other diseases.Review articles, editorials, clinical guidelines, studies that reported patients with either MG or LP (but not both), and any articles that did not align with our research question were excluded.No prior restrictions were imposed on study design (except for review articles, editorials, and guidelines), country, publication year, participant age, or any other factors.

| Selection process
Initially, data records were imported into the EndNote software (version X9, Clarivate Plc) from various databases.Following the removal of duplicates, two separate researchers (M.J. and M.A.) reviewed all the records based on their titles and abstracts.The full texts of records that seemed potentially eligible were then evaluated further by three independent researchers (M.J., M.A., and B.A.).Any records that didn't meet the predefined eligibility criteria were excluded.Disagreements were settled by achieving a consensus.

| Data collection
The following data were extracted for each study: studyrelated variables (authors and published year), populationrelated variables (age, sex, past medical history [PMH], and other immune-related comorbidities), as well as MGand LP-related variables (symptoms and signs, age at diagnosis, treatment, and outcome).

| Case presentation
A 67-year-old man, who was diagnosed with LP1 year ago, was admitted to the hospital whose symptoms had initiated 20 days before.The earliest symptom was mild bilateral ptosis.Progressive dysphagia and dysarthria were gradually added during the disease.In the beginning, the patient suffered from dysphagia to solids which progressed to dysphagia to liquids 3 days before attending the hospital.He developed dysarthria almost simultaneously with dysphagia in the form of nasal speech and unintelligible words, worsening with prolonged talking.However, his ability to understand was intact.The patient reported that his symptoms were milder in the morning and exacerbated during the afternoon.He did not report any difficulty in breathing.As well, he did not mention any other associated symptoms, such as headaches, diplopia, blurred vision, vertigo, dizziness, ataxia, or gastrointestinal symptoms.His medical history included primary hypertension, diabetes mellitus type 2, as well as multiple rapidly spreading purplish and pruritic lesions, which had been diagnosed as generalized LP a year before.There was no history of recent travel or infection or any particular food intake.Family and habitual history were unrevealing.
The initial physical examination showed an elderly, alert, and oriented male, without any signs of respiratory distress.He answered the questions cooperatively, albeit incomprehensible due to dysarthria.Vital signs were overall stable: T = 37.1°C, BP = 124/85 mmHg, HR = 87 beats per minute, RR = 14 breaths per minute, and O 2 saturation in the room air = 98%.Flat-topped, polygonal, violaceus papules were found all over the skin.Additionally, hyperpigmented macules and cutaneous eruptions were evident, particularly on the flexural surfaces of the lower extremities.There were no signs of mucous membranes, genitalia, nails, hair, or scalp involvement.Neurologic examinations revealed asymmetric bilateral fatigable ptosis with no evidence of ophthalmoplegia.There were no signs of facial asymmetry or sensory deficit.The gag reflex was severely decreased.The uvula was not deviated, and the soft palate elevation was symmetric.No signs of tongue deviation or fasciculation were present.The motor examination revealed fatigability and weakness in the proximal muscles of the upper and lower extremities (Table 1).Deep tendon reflexes (DTR), the superficial abdominal reflex, and plantar reflexes on both sides were normal.The remainder of the physical examination, including sensory-neural and cerebellar examinations, did not disclose any other abnormalities.
An electrocardiogram (ECG) showed normal sinus rhythm.The initial patient's laboratory tests showed no abnormality (Table 2).In the following days, a comprehensive autoimmune workup was performed; rheumatologic laboratory tests and thyroid function tests were performed to rule out systematic lupus erythematosus (SLE), rheumatoid arthritis (RA), and Graves' disease.MG-specific tests, including anti-AchR and anti-MuSK-Abs, were performed, with a positive titer of 5.43 nmol/L for anti-AchR-Ab and negative results for anti-MuSK-Ab.The patient was diagnosed with late-onset seropositive class "IVb" MG.The treatment included pyridostigmine (60 mg, three times daily) and IVIG (25 g daily for 5 days).Additionally, 50 mg oral prednisolone was initiated.
Chest x-ray (CXR) revealed no abnormality.Since a negative CXR does not rule out small thymomas, a chest CT scan was required. 1As the patient's condition worsened and dysphagia progressed, he was admitted to the intensive care unit (ICU).Due to the patient's unstable condition, contrast was not used for the chest CT scan, which showed no signs of thymoma or other abnormalities.MRI of the brain and orbit was unraveling.Routine motor and sensory nerve conduction studies (NCS), routine needle electromyography (EMG) of distal and proximal muscles, and compound muscle action potential (CMAP) revealed no abnormal findings.Repetitive nerve stimulation (RNS) of muscles at 3 Hz showed a decremental response in the anconeus, trapezius, and orbicularis oculi muscles, with reduced excitatory postsynaptic potentials (EPSPs) (Table 1).

| Systematic literature search and study selection
The PRISMA flowchart provides a visual representation of the inclusion process (Figure 1).Searching the databases resulted in 196 records.After duplication removal, 150 records were screened by titles and abstracts, of which 95 articles were excluded.Of the remaining 55 articles sought for retrieval, the full text of one article was not retrieved, 34 and one additional study was found by manual search. 35Therefore, 55 studies were assessed for eligibility, 42 of which were excluded for the following reasons: having either MG or LP (not both) or other autoimmune diagnoses (i.e., Good's syndrome, SLE, autoimmune thyroiditis, thymoma-associated multiorgan autoimmunity [TAMA], autoimmune atrophic gastritis, paraneoplastic pemphigus, adverse drug reactions, thymoma-associated graft-versus-host disease [GVHD]-like erythroderma, etc.) (n = 40), and non-English articles (n = 2). 38,39Eventually, 13 articles were included in this systematic review.

| DISCUSSION
In this study, we described a patient with concomitant MG and LP and no evidence of thymoma.Previously, the association between MG and LP has been reported in a few cases.We reviewed a variety of patients based on the studies published between 1971 and 2024.Most patients had LP, MG, and thymoma together, but some only had LP and MG.In 1974, Tan et al. reported the subsequent events experienced by this patient; he developed alopecia areata a year after MG diagnosis, and vitiligo also appeared 3 years later. 30In 1997, Giménez-Arnau et al. introduced two patients who experienced the coexistence of MG and LP. 21The first patient was a 60-year-old female with an incidentally diagnosed thymoma who developed oral LP and generalized seropositive MG, 1 year and 2 years after thymoma detection, respectively.The second patient was diagnosed with ocular MG at the age of 65, followed by developing LP lesions 2 years later.Further evaluations of this patient revealed no signs of thymoma. 21he authors mentioned two possible conclusions.First, the association of MG and LP in both cases could support their common autoimmune nature.Second, the presence of thymoma in the first case and the absence of that in the second patient could suggest that thymoma could not act as a primary event in MG. 21Consistently, in 2023, Ho et al. introduced a 67-year-old male presented with left head tilt associated with right eye hypertropia on the straightening of his head. 41Ophthalmology tests revealed fatigable ptosis of eyelids, as well as a positive Cogan's lid twitch sign.
The patient was diagnosed with ocular MG and showed improvement with pyridostigmine.Three months later, he noticed a hyperpigmented, purplish patch at his back, along with several hyperpigmented streaks in both axillae and erythematous macules on the chest.The patient finally developed several hyperpigmented macules at the trunk and was diagnosed with lichen planus pigmentosusinversus.Topical betamethasone valerate was prescribed, and in subsequent follow-up, the lesions didn't show progression and remained the same.There was no evidence of thymoma detected.

co-occurrence with thymoma
Recent studies showed that MG could be a part of a paraneoplastic syndrome associated with thymoma. 44,45n 1978, Aronson et al. reported a 54-year-old woman who developed MG followed by LP a year later. 20 thymoma.Simultaneously, as the initial symptoms of MG appeared, LP lesions became evident. 22In 1994, Helm et al. introduced a 60-year-old woman with metastatic breast cancer who had had benign thymoma along with MG 7 years earlier, treated with surgical extirpation and low-dose prednisone.Since then, the patient experienced an oral erosive disease, presenting with long linear erosions on the tongue as well as lower labial mucosa which was diagnosed as LP through biopsy.The symptoms were finally controlled with prednisone and griseofulvin. 35n 1996, Mineo et al. described a 32-year-old woman who underwent splenectomy due to ITP in 1988. 36She was also diagnosed with oral LP.In February 1995, she presented with petechia and MG symptoms.Her symptoms well responded to plasmapheresis, pyridostigmine bromide, and prednisone.She also showed psychiatric symptoms including gustatory and olfactory hallucinations, dysphoria, and recent memory loss.Of note, she was diagnosed with thymoma which was excised and did not show recurrence following the operation.Interestingly, her LP-associated oral lesions disappeared 2 months after the operation; therefore, steroids were discontinued.Furthermore, psychiatric symptoms improved 4 months after surgery.In 2015, Motegi et al. evaluated 50 patients with LP referred to their clinic between 2004 and 2014, identifying thymoma in three (6%) individuals.Among them was a 50-year-old male with erosive oral LP, who had    The simultaneous occurrence of MG and lichen planus LP suggests underlying shared pathophysiological mechanisms that could include disruptions in immune function (i.e., T cell dysfunction), genetic vulnerabilities, and environmental triggers (i.e., infectious diseases). 20he thymus gland plays a critical role in both disorders.It provides a vital environment for T-cell development, essential for immune surveillance and the prevention of autoimmune reactions. 46The process of thymopoiesis ensures a full complement of peripheral naïve T cells capable of diverse pathogen recognition, as well as regulatory T cells capable of suppressing hyperactive immune responses and autoimmunity. 467][48] This may explain why some patients with MG and LP exhibit thymic involvement, while others do not.While the specific mechanisms of peripheral T cell turnover (outside the thymus) remain unclear, recent studies suggest lymph nodes might act as a tissue reservoir for naïve and resting T cell maintenance. 47,491][52][53][54] For instance, variations within the human leukocyte antigen (HLA) region, also known as the major The patient was diagnosed with lichen planus pigmentosus, which is a variant of lichen planus.

Baseline demographic and clinical characteristics
c The skin manifestations are related to both pemphigus vulgaris and lichen planus.
T A B L E 3 Continued histocompatibility complex (MHC), are associated with a higher risk of developing MG. 50,51Similarly, variants in the IL-12/23 and IL-17 receptor genes have been linked to an increased risk of LP. 52,53 Interestingly, the cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene appears to play a role in both MG and LP, further suggesting that these conditions may share common underlying mechanisms. 51,54,557][58] It is suggested that molecular mimicry is one of the principal mechanisms that foreign antigens lead to autoimmunity. 57,59This occurs when cross-reactive epitopes are displayed via the MHC, leading to an immune response through T-cell activation. 57,59e resulting proinflammatory response, crucial for eliminating pathogens, may continue if there is a sequential or structural similarity between foreign and self-antigens. 59n the other hand, the CTLA-4 is a co-inhibitory molecule that plays a critical role in dampening immune responses to avoid autoimmunity, by suppressing T-cell activation, proliferation, and cytokine production. 60Therefore, CTLA-4 deficiency or mutation can lead to autoimmune diseases. 60However, while these genetic variations may suggest overlapping genetic predispositions that contribute to autoimmunity, further research is required in this regard.
Environmental factors also play a role, with both conditions possibly being influenced by variables such as smoking, 61,62 socioeconomic factors, 61,63 stress, 64 viral infections, 53,64 and exposure to certain chemicals or drugs. 53,64Overall, a combination of immune system dysfunction, genetic predisposition, and environmental factors, determines an individual's overall susceptibility to these autoimmune conditions.

| Thymoma and autoimmune disorders: Possible mechanisms and associations
MG occurs in 50% of patients with thymoma (varying from 7% to 54% 65 ), and is called thymoma-associated MG (TAMG) in these cases. 66Notably, a multicenter retrospective study found a poorer prognosis for patients with TAMG compared to non-thymoma MG. 67 On the other side, approximately 10%-20% of patients with MG develop thymoma. 28,68According to previous studies, thymoma has the greatest rate of paraneoplastic syndromes among all human cancers. 65The term "paraneoplastic syndrome" refers to a group of rare diseases with multiple systemic manifestations caused by an impaired immune response due to an underlying malignancy. 69Indeed, T cells generated by the neoplastic thymoma tissue are likely to be responsible for the autoimmune paraneoplastic features. 70onsistently, in 2011, Qiao et al. reported a 53-year-old male with a 6-month history of myasthenic symptoms and oral mucosal lesions, which were diagnosed as LP after a buccal biopsy. 23A CT scan showed an anterior mediastinal mass, indicative of thymoma.Seven months after initiating treatment, he presented with scalp alopecia and vitiligo.Notably, his oral lesions, unresponsive to medical treatment, improved significantly 1 month after thymectomy. 23his finding aligns with reports of other patients experiencing remarkable improvement in symptoms of MG 22 or LP 36 after thymectomy.Contrarily, while the patient reported by Aronson et al. experienced some initial improvement in the mucocutaneous lesions several weeks following thymectomy, the lesions became worsened and more widespread only after a few weeks. 20Nevertheless, current guidelines support thymectomy as a treatment for MG due to its potential for improved clinical outcomes and long-term benefits. 13Studies have shown that thymectomy roughly doubles the chance of achieving medication-free remission and increases the likelihood of becoming symptom-free by about 50%. 13However, it's important to note that the full benefits of thymectomy may take several years to develop. 13Notably, the role of thymectomy in improving LP has not yet been established and requires further research. 27,71,72n 2021, Bendayan et al. reported a case presenting with generalized lichenoid plaques. 42The patient was previously diagnosed with MG, Good's syndrome, T-cell large granular lymphocyte leukemia, and malignant thymoma which had been resected multiple times.Of note, biopsy results revealed infiltration of CD8 + and CD4 + lymphocytes (with dominance of CD8 + cells), dyskeratosis, extensive pigmentary incontinence, as well as thickened collagen bundles in the dermis and the subcutaneous layer.Based on clinical and paraclinical findings, chronic GVHD, LP, and morphea in the setting of TAMA were considered differential diagnoses.Finally, according to the presence of malignant thymoma in the patient's history, TAMA was favored over the other differential diagnoses. 42TAMA is a rare paraneoplastic disease that is characterized by the involvement of the gastrointestinal tract, thyroid, and liver, as well as skin. 71,73he underlying pathophysiology of TAMA is supposed to be the thymoma's contribution to the disruption of the thymus function in developing central tolerance and negative selection. 42Consistently, according to a study by Offerhaus et al., patients with TAMA showed decreased expression of autoimmune regulator genes (AIRE) which are expressed by the thymus and contribute to the negative selection of T cells. 74Consistently, Hoffacker et al. detected elevated levels of CD8 + autoantigen-specific T cells in the blood of patients with thymoma. 75Taken together, the above-mentioned hypotheses could explain the association of thymoma with several paraneoplastic and autoimmune disorders such as MG, lichenoid skin lesions, hypogammaglobulinemia, pure red cell aplasia, and RA. 28,42,76,77he co-existence of MG and LP has been also reported in the context of multiple autoimmune syndrome (MAS), 43 as exemplified by the case reported by Ge et al.This involved a 64-year-old female with MAS, who underwent thymectomy 22 years prior and was subsequently diagnosed with an array of autoimmune conditions, including pemphigus vulgaris, MG, vitiligo, pure red cell aplasia, systemic lupus erythematosus, LP, and alopecia areata. 43

| Limitations and strengths
Although a contrast-enhanced chest CT is essential for thymoma evaluation, the patient's instability necessitated reliance on a non-contrast chest CT.The robustness of this study is enhanced by an exhaustive review of the pertinent literature from its origin to the present.

DIRECTIONS
While the exact pathogenesis of MG, LP, and thymoma co-occurrence remains elusive, it suggests the possibility of a shared autoimmune mechanism.Various theories have been suggested to explain the association between thymoma and autoimmune disorders or paraneoplastic syndromes due to T lymphocyte dysfunction, genetic predisposition, and environmental factors.Nonetheless, instances of MG and LP co-occurring without thymoma suggest that these conditions might arise independently of paraneoplastic syndromes.This supports the notion that a dysregulated immune response could account for the simultaneous presence of multiple autoimmune diseases within an individual.
Several key questions remain regarding the coexistence of MG and LP.Future research should delve deeper into the role and mechanisms of peripheral T-cell homeostasis, particularly in patients without thymoma.Understanding how the body maintains T-cell balance outside the thymus could shed light on the shared pathological mechanisms between these conditions.Additionally, further investigation is needed to elucidate the specific genetic variations that increase susceptibility to MG and LP.Prospective studies are crucial to definitively determine the role of thymectomy in improving LP.Understanding how thymoma disrupts the thymus's ability to develop central tolerance and negative selection of T cells also requires further exploration.These areas of research hold promise for improving our understanding of MG and LP, both with and without thymoma involvement.Ultimately, this knowledge could lead to the development of enhanced diagnostic tools, including specific biomarkers for early detection of MG and LP.Additionally, it may inform more effective therapeutic strategies, encompassing both established and potentially novel treatment approaches for these autoimmune conditions.
In conclusion, patients with MG, LP, or thymoma require close follow-up and evaluation for other potential disorders, particularly autoimmune diseases.

T A B L E 1
Abbreviations: CMAP, compound muscle action potentials; EMG, electromyography, NCS, nerve conduction studies, RNS, repetitive nerve stimulation.a Scoring is based on the Medical Research Council (MRC) scale.

4. 2 |
Individuals with MG and LP

F I G U R E 1 37 T A B L E 3
PRISMA 2020 flow diagram for new systematic reviews.From: Page MJ, et al.Cases reported in the literature with coexistence of MG and LP up till February 01, 2024.

4.1 | Individuals with MG and LP co-occurrence without thymoma
In 1971, Miller et al. reported a 35-year-old man who developed UC, followed by LP 4 years later.Nine years after LP diagnosis, he presented ocular symptoms of MG, and a period of severe relapse and respiratory failure occurred in the same year.
Patient laboratory evaluations.